Prostate cancer is the most common noncutaneous cancer in males and the second most common cause of cancer-related death in men in the United States (Jemal et al. (2008) CA Cancer J. Clin. 58:71-96). The American Cancer Society estimates that in 2009, 92,280 new cases of prostate cancer will be diagnosed and 27,360 men will die of prostate cancer. The incidence of prostate cancer diagnosis in men exceeds 1 in 6, and the death rate due to prostate cancer is approximately 1 in 35. Standard treatment of advanced and/or metastatic prostate cancer includes androgen suppression, cytotoxic chemotherapy, and radiation. These treatment modalities carry significant side effects, and treatment regimes (and consequently likelihood of success) are far more limited for hormone-refractory prostate tumors than hormone-responsive tumors. For metastatic prostate cancer, no form of therapy is curative, and thus this represents a terminal diagnosis. Surgical approaches and radiation, typically in combination with hormone therapy, may be used for intermediate-stage tumors; however, again, these modalities carry significant risk of undesirable side effects such as incontinence and/or impotence. For early-stage tumors, standard approaches consist of surgery, radiation (which may be combined with hormone therapy) or watchful waiting. With watchful waiting, consensus guidelines related to its implementation are lacking, changes in clinical parameters with time lead to frequent repetitive biopsies, and with the knowledge that they have confirmed prostate cancer patients experience high levels of anxiety. All of these factors contribute to a channeling of patients into eventual treatment with surgery or radiation.
microRNAs (miRNAs, miRs) are endogenous non-coding small RNA's that interfere with the translation of coding messenger RNAs (mRNAs) in a sequence-specific manner, playing a critical role in the control of gene expression during development and tissue homeostasis (Yi et al., Nat Genet 2006; 38:356-362). Certain miRNAs have been shown to be deregulated in human cancer, and their specific over- or under-expression has been shown to correlate with particular tumor types (Calin and Croce, Nat Rev Cancer 2006; 6:857-866), as well as to predict patient outcome (Yu et al., Cancer Cell 2008; 13:48-57). In some cases miRNA over-expression results in reduced expression of tumor suppressor genes, while loss of miRNA expression often leads to oncogene activation.
Significant associations have been demonstrated between expression of miRNA signatures and clinical outcome of lung adenocarcinoma, chronic lymphocytic leukemia, breast and pancreatic cancers.
Prognosis and staging of prostate cancer is an important tool in weighing the efficacy and cost-effectiveness of alternative treatments. Any improvement in prognostic tools will enable better treatment of those in need, increasing their chances of a full cure and/or increasing their life expectancy, as well as quality of life. While a mere shift in the threshold for decisions on treatment may assign more patients to seemingly life-extending treatment regimens, these carry the increased risk of unpleasant and potentially life-threatening side-effects for patients who would not benefit from the treatment, or for those who should be assigned alternative protocols or none at all.
The prognosis for prostate is influenced by the stage of the disease. Surgery, when performed as part of a multimodality therapy with cytotoxic chemotherapy and radiation therapy, can be effective treatment, but only in the rare event of an early stage diagnosis. Accordingly, there is a great need for more sensitive and accurate methods for the prognosis of prostate cancer in a human to determine whether or not such cancer will become aggressive (will metastasize).
Thus, there exists a need for identification of biomarkers that can be used as prognostic indicators for prostate cancer.
Better treatment of prostate cancer is also needed. In particular, agents that prevent prostate cancer metastasis are needed.